Oncogenic miR-137 contributes to cisplatin resistance via repressing CASP3 in lung adenocarcinoma

Te Jen Su, Wen Hui Ku, Hsuan Yu Chen, Yi Chiung Hsu, Qi Sheng Hong, Gee Chen Chang, Sung Liang Yu, Jeremy J.W. Chen

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Although targeted therapy can prolong the survival of non-small cell lung cancer (NSCLC) patients with EGFR mutations, chemotherapy still is the choice for patients with wild-type EGFR or failure in targeted therapy. However, most of the patients will eventually develop chemoresistance. Our previous study showed that miR-137 is a risky microRNA and is associated with poor prognosis in NSCLC patients. Here we investigated the role of miR-137 in cisplatin resistance in lung adenocarcinoma patients. Our data indicated that miR-137 overexpression increases the survival of lung cancer cells exposed to cisplatin and decreases cisplatin-induced apoptosis. Through computational prediction and microarray, we identified caspase-3 (CASP3) as a potential target of miR-137. Luciferase reporter and site-directed mutagenesis assays demonstrated that miR-137 downregulates CASP3 through binding to its 3'-UTR. Moreover, the endogenous CASP3 can be modulated by overexpressing or silencing miR-137 in lung adenocarcinoma cell lines regardless of EGFR status. Suppression of CASP3 by miR-137 provides cancer cells with anti-apoptotic ability, leading to cisplatin resistance. Immunohistochemistry results revealed an inverse correlation between miR-137 and CASP3 expressions in lung adenocarcinoma patients. Together, our data provide a new chemoresistance mechanism in lung adenocarcinoma and a possible target to control chemoresistance in lung adenocarcinoma patients.

Original languageEnglish
Pages (from-to)1317-1330
Number of pages14
JournalAmerican Journal of Cancer Research
Issue number6
StatePublished - 2016


  • Caspase 3
  • Chemoresistance
  • Cisplatin
  • Lung adenocarcinoma
  • MiR-137


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